651-665Head and neck squamous cell carcinoma
(HNSCC), a common malignancy that possibly involves a combination of exposure
to the carcinogens and inherited genetic differences in the enzymes catalyzing
their metabolism. Alcohol and tobacco consumption are the primary environmental
risk factors, while polymorphism in various biotransformation enzymes such as
cytochrome P450s (CYPs) and glutathione S-transferases, (GSTs) has been
implicated as the major genetic risk factors for the development of HNSCC. The
functionally important polymorphisms in these CYPs (1A1*2A, 1A1*2C,
1B1*2, 2E1*5B, 2E1*6, 2C19*2, 2D6*4, 2D6*10)
and GSTs (GSTM1-null or GSTT1-null) were found to be significantly
associated with HNSCC risk. Significant differences in the distribution of certain
haplotypes of CYPs have also been reported and prevalence of certain genotype
combinations of CYPs and GSTS in cases has indicated the importance of
gene-gene interactions in HNSCC risk. Alcohol or tobacco use (smoking and
chewing) were also found to interact synergistically with variant genotypes of
these CYPs and GSTS in significantly enhancing HNSCC risk. This increase in
risk associated with the variant genotypes with tobacco or alcohol use have
further demonstrated the importance of gene–environment interactions in determining
the susceptibility to HNSCC.</b